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Cited by 293

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.

Major genetic marker of nidoviruses encodes a replicative endoribonuclease

Open access
Ivanov, Konstantin A., Hertzig, Tobias, Rozanov, Mikhail, Bayer, Sonja, Thiel, Volker, Gorbalenya, Alexander E., Ziebuhr, John·2004·Proceedings of the National Academy of Sciences

Abstract

Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the ≈30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses ( Coronaviridae, Arteriviridae , and Roniviridae ) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn 2+ -dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2′-3′ cyclic phosphate ends. 2′- O -ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2′- O -ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.

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Metadata

Authors
Ivanov, K. A., Hertzig, T., Rozanov, M., Bayer, S., Thiel, V., Gorbalenya, A. E., & Ziebuhr, J.
Venue
Proceedings of the National Academy of Sciences
Published
2004-08-10
Volume
101
Issue
34
Pages
12694-12699
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2138929325
Cited by
293
References
22
FWCI
29.51
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Major genetic marker of nidoviruses encodes a replicative endoribonuclease. https://app.cochat.ai/papers/10.1073/pnas.0403127101
The paper
Ivanov, K. A., Hertzig, T., Rozanov, M., Bayer, S., Thiel, V., Gorbalenya, A. E., & Ziebuhr, J. (2004). Major genetic marker of nidoviruses encodes a replicative endoribonuclease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0403127101

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